Carboxyalkylethers, formulations, and treatment of vascular diseases

Abstract

Dialkyl ethers lower Lp(a) and triglycerides, and elevate HDL-cholesterol, and are thereby useful for treating vascular diseases and noninsulin-dependent diabetes mellitus.

We claim: 
     
       1. A method for lowering plasma Lp(a) comprising administering to a mammal an Lp(a) lowering amount of a compound of the formula ##STR13## wherein n and m independently are integers fom 2 to 9; R 1 , R 2 , R 3 , and R 4  independently are C 1  -C 6  alklyl, C 2  -C 6  alkenyl, C 2  -C 6  alkynyl, and R 1  and R 2  together with the carbon to which they are attached, and R 3  and R 4  together with the carbon to which they are attached, independently can complete a carbocyclic ring having from 3 to 6 carbons;   Y 1  and Y 2  independently are COOH, CHO, tetrazole and COOR 5  where R 5  is C 1  -C 6  alky, C 2  -C 6  alkenyl, C 2  -C 6  alkynyl; and where the alkyl, alkenyl, and alkynyl groups may be substituted with one or two groups selected from halo, hydroxy, C 1  -C 6  alkoxy, and phenyl, and the pharmaceutically acceptable salts theref.   
     
     
       2. The method of claim 1 employing 6,6'-oxybis(2,2-dimethylhexanoic acid). 
     
     
       3. A method for lowering apolipoprotein B comprising administering to a mammal an effective amount of a compound of the formula ##STR14## wherein n and m independently are integers from 2 to 9; R 1 , R 2 , R 3 , and R 4  independently are C 1  -C 6  alkyl, C 2  -C 6  alkenyl, C 2  -C 6  alkynyl, and R 1  and R 2  together vith the carbon to which they are attached, and R 3  and R4 together with the carbon to which they are attached, independently can complete a carbocyclic ring having from 3 to 6 carbons;   Y 1  and Y 2  independently are COOH, CHO, tetrazole, and COOR 5  where R 5  is C 1  -C 6  alkyl, C 2  -C 6  alkenyl, C 2  -C 6  aIkynyl; and where the alkyl, alkenyl, and alkynyl groups may be substituted with one or two groups selected from halo, hydroxy, C 1  -C 6  alkoxy, and phenyl, and the pharmaceutically acceptable salts thereof.     
     
     
       4. The method according to claim 3 employing 6,6'-oxybis(2,2-dimethylhexanoic acid). 
     
     
       5. A method of elevating plasma apolipoprotein A-1 comprising administering to a mammal an effective amount of a compound of the formula ##STR15## wherein n and m independently are integers from 2 to 9; R 1 , R 2 , R 3  and R 4  independently are C 1  -C 6  alkyl, C 2  -C 6  alkenyl, C 2  -C 6  alkynyl, and R 1  and R 2  together with the carbon to which they are attached, and R 3  and R 4  together with the carbon to which they are attached, independently can complete a carbocyclic ring having from 3 to 6 carbons;   Y 1  and Y 2  independently are COOH, CHO, tetrazole , and COOR 5  where R 5  is C 1  -C 6  alkyl, C 2  -C 6  alkenyl, C 2  -C 6  alkynyl; and where the alkyl, alkenyl, and alkynyl groups may be substituted with one or two groups selected from halo, hydroxy, C 1  -C 6  alkoxy, and phenyl, and the pharmaceutically acceptable salts thereof.     
     
     
       6. The method of claim 5 employing 6,6'-oxybis(2,2-dimethylhexanoic acid). 
     
     
       7. A method of elevating plasma apolipoprotein E comprising administering an effective amount of a compound of the formula ##STR16## wherein n and m independently are integers from 2 to 9; R 1 , R 2 , R 3 , and R 4  independently are C 1  -C 6  alyl, C 2  -C 6  alkenyl, C 2  -C 6  alkynyl, and R 1  and R 2  together with the carbon to which they are attached and R 3  and R 4  together with the carbon to which they are attached, indeperdently can complete a carbocyclic ring having fom 3 to 6 carbons;   Y 1  and Y 2  independently are COOH, CHO, tetrazole, and COOR 5  where R 5  is C 1  -C 6  alkyl, C 2  -C 6  alkenyl , C 2  -C 6  alkynyl; and where the alkyl, alkeny, and alkynyl groups may be substituted with one or two groups selected from halo, hydroxy, C 1  -C 6  alkoxy, and phenyl, and the pharmaceuticaliy acceptable salts thereof.     
     
     
       8. The method according to claim 7 employing 6,6'-oxybis(2,2-dimethylhexanoic acid).